1. Distinct Properties of Cell-Type-Specific and Shared Transcription Factor Binding Sites.
- Author
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Gertz, Jason, Savic, Daniel, Varley, Katherine?E., Partridge, E.?Christopher, Safi, Alexias, Jain, Preti, Cooper, Gregory?M., Reddy, Timothy?E., Crawford, Gregory?E., and Myers, Richard?M.
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TRANSCRIPTION factors , *BINDING sites , *ESTROGEN receptors , *DNA methylation , *CHROMATIN , *GENETIC regulation - Abstract
Summary: Most human transcription factors bind a small subset of potential genomic sites and often use different subsets in different cell types. To identify mechanisms that govern cell-type-specific transcription factor binding, we used an integrative approach to study estrogen receptor α (ER). We found that ER exhibits two distinct modes of binding. Shared sites, bound in multiple cell types, are characterized by high-affinity estrogen response elements (EREs), inaccessible chromatin, and a lack of DNA methylation, while cell-specific sites are characterized by a lack of EREs, co-occurrence with other transcription factors, and cell-type-specific chromatin accessibility and DNA methylation. These observations enabled accurate quantitative models of ER binding that suggest tethering of ER to one-third of cell-specific sites. The distinct properties of cell-specific binding were also observed with glucocorticoid receptor and for ER in primary mouse tissues, representing an elegant genomic encoding scheme for generating cell-type-specific gene regulation. [Copyright &y& Elsevier]
- Published
- 2013
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